Investigations
1st investigations to order
FBC
Test
Ordered at baseline and regular intervals in all patients with metastatic breast cancer.
Blood tests (including FBC, LFTs, and calcium) can help to determine if a patient can tolerate chemotherapy or is a suitable candidate for another systemic therapy. They may occasionally help indicate sites of metastasis. For example, abnormal FBC may indicate bone or liver metastasis.
Result
may be normal; abnormal findings may indicate bone or liver disease
LFTs
Test
Ordered at baseline and regular intervals in all patients with metastatic breast cancer.
Blood tests (including FBC, LFTs, and calcium) can help to determine if a patient can tolerate chemotherapy or is a suitable candidate for another systemic therapy. They may occasionally help indicate sites of metastasis. For example, abnormal LFTs may indicate bone or liver metastasis.
Result
may be normal; abnormal findings (e.g., elevated alkaline phosphatase or generalised derangement of liver enzymes) may indicate bony metastases or massive metastases to liver
calcium
Test
Ordered at baseline and regular intervals in all patients with metastatic breast cancer.
Blood tests (including FBC, LFTs, and calcium) can help to determine if a patient can tolerate chemotherapy or is a suitable candidate for another systemic therapy. They may occasionally help indicate sites of metastasis. For example, elevated calcium (hypercalcaemia) may indicate bone metastasis.
Result
may be normal; elevated calcium (hypercalcaemia) may indicate bone disease
CT (of chest and abdomen)
Test
Ordered at baseline (and regular intervals thereafter) in all patients with metastatic breast cancer to detect metastatic lesions and for staging.[28][46]
Imaging should focus on symptomatic areas.
Chest CT may also detect pleural effusion. Cytological assessment of the effusion can determine if malignant cells are present.
Imaging studies used for initial metastatic work-up should also be used for monitoring disease and assessing treatment response.[28]
Result
may show abnormal mass (e.g., lung or liver metastases); pleural effusion
bone scan (scintigraphy)
Test
Ordered at baseline and when patients develop bone pain or have abnormal blood tests (FBC, LFTs, calcium) suggesting bone metastasis.[46]
Imaging should focus on symptomatic areas.
Bone scans are sensitive for osteoblastic lesions.[50]
Imaging studies used for initial metastatic work-up should also be used for monitoring disease and assessing treatment response.[28]
Result
may show abnormal bone lesions indicating metastases
Investigations to consider
MRI (focused on area of concern, e.g., brain, spinal cord, bone)
Test
MRI is often preferred over CT to detect metastatic lesions in the brain, spinal cord, and specific areas in bone.[28][46][49]
MRI of the brain and spinal cord should be carried out only if there are signs or symptoms suggesting central nervous system or spinal metastasis.[28][46]
Imaging studies used for initial metastatic work-up should also be used for monitoring disease and assessing treatment response.[28]
Result
may show abnormal lesions indicating metastases
FDG-PET/CT scan
Test
May be considered instead of a bone scan.[28][46] PET/CT scan is sensitive for osteolytic lesions.[50]
FDG-PET/CT scan may be preferred to CT or MRI, or used in conjunction with these imaging modalities if their results are equivocal.[28][46]
Imaging studies used for initial metastatic work-up should also be used for monitoring disease and assessing treatment response.[28]
Result
may show abnormal lesions indicating metastases
biopsy of metastatic lesion
Test
Confirms nature of lesion.
When technically feasible and easily accessible, biopsy of the metastatic lesion should be carried out to confirm the diagnosis (histologically) and to assess tumour biomarker status (e.g., hormone [oestrogen, progesterone] receptor status, and human epidermal growth factor receptor 2 [HER2] status), which can inform prognosis and guide treatment (e.g., endocrine therapy, HER2-targeted therapy).[28][46][55][56]
Hormone receptor discordance between the primary tumour and the metastatic site may be considerable (10% to 30% for oestrogen receptor status and 20% to 50% for progesterone receptor status).[57] Also, oestrogen receptor status may change from positive to negative over time.
In the presence of discordance, it is preferable to treat according to the receptor status of the metastatic lesion, if supported by the clinical scenario and patient's goals for care.[58]
Result
may be positive or negative for oestrogen receptor, progesterone receptor, and HER2
high-penetrance breast cancer susceptibility genes
Test
Patients with metastatic breast cancer should be tested for high-penetrance breast cancer susceptibility genes (BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, and TP53).[22][28] Mutations in these genes can inform prognosis and guide treatment.
BRCA1 and BRCA2 germline mutations are the most common cause of hereditary breast cancer.[21]
Testing for BRCA1 and BRCA2 germline mutations is required to identify those eligible for poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor therapy.[22][28][46]
Result
may identify genetic mutations that can inform prognosis and guide treatment
additional biomarker testing
Test
Testing for the following biomarkers may also be considered to guide treatment: PIK3CA mutation (for phosphatidylinositol 3-kinase inhibitor therapy), PD-L1 expression (for immune checkpoint inhibitor therapy), and ESR1 mutation (for selective oestrogen receptor modulator/degrader therapy).[28][46][58][59]
Patients may undergo testing for the following biomarkers if treatment with an immune checkpoint inhibitor or tyrosine receptor kinase inhibitor is being considered: dMMR/MSI (deficient mismatch repair/microsatellite instability, for immune checkpoint inhibitor therapy); TMB (tumour mutational burden, for immune checkpoint inhibitor therapy); NTRK fusions (for tyrosine receptor kinase inhibitor therapy); and RET fusions (for tyrosine receptor kinase inhibitor therapy).[28][46][58]
Elevated serum biomarkers (cancer antigen 15-3 [CA 15-3], cancer antigen 27.29 [CA 27.29], and carcinoembryonic antigen [CEA]) may be concerning for disease progression, but may also occur during disease response.[46]
Biomarkers may be used in conjunction with other evaluations, but not alone, to guide therapy.[58]
Result
may identify biomarkers that can inform prognosis and guide treatment
echocardiogram
Test
Evaluation of ventricular function should be carried out if treatment with doxorubicin or trastuzumab is being considered. These drugs are potentially cardiotoxic and can cause a decline in ejection fraction.[52][53][54]
An echocardiogram will give a baseline cardiac function before treatment is started. If cardiac function is not adequate, use of doxorubicin or trastuzumab is not appropriate.
Echocardiogram can be repeated once treatment is completed.
Result
normal; or decline in cardiac function
multi-gated acquisition (MUGA) scan
Test
Evaluation of ventricular function should be carried out if treatment with doxorubicin or trastuzumab is being considered. These drugs are potentially cardiotoxic and can cause a decline in ejection fraction.[52][53][54]
A MUGA scan will give a baseline cardiac function before treatment is started. If cardiac function is not adequate, use of doxorubicin or trastuzumab is not appropriate.
MUGA scan can be repeated once treatment is completed.
Result
normal; or decline in cardiac function
pleural cytology
Test
Pleural effusion found on CT scan requires cytological assessment to determine if malignant cells are present.
Result
presence of malignant cells; negative pleural cytology does not, however, exclude a malignant pleural effusion
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